On January 30, 2020 GlycoMimetics, Inc. (Nasdaq: GLYC) reported that Duke University investigators have dosed the first patient in a proof-of-concept Phase 1b study to evaluate GlycoMimetics’ novel GMI-1359 drug candidate in patients with advanced breast cancer (Press release, GlycoMimetics, JAN 30, 2020, View Source [SID1234553700]). The dose-escalating study will enroll up to 12 individuals with metastatic, hormone receptor positive breast cancer with stable or minimally progressive disease, including bone metastasis. GMI-1359 is a dual inhibitor of both E-selectin and CXCR4. The trial is designed to evaluate safety, pharmacokinetics and pharmacodynamic measures of biologic activity, such as increases in circulating tumor cells and mobilization of CD34+ and immune T-cell subsets. GlycoMimetics expects the trial results to be available in late 2020, the conclusions of which the Company will use to inform future development of GMI-1359.

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Kelly Marcom, M.D., and Dorothy Sipkins, M.D., Ph.D., both of the Duke Cancer Institute, are the trial’s co-principal investigators.This clinical trial builds on published findings from Dr. Sipkins on the key roles of both E-selectin and CXCR4 in the trafficking of metastatic cancer cells and of their establishment as micro-metastases in bone. Dr. Sipkins’ research suggests that both E-selectin and CXCR4 mediate key mechanisms that promote progression and migration of cancer cells to protective niches in the bone marrow micro-environment, and reveals the potential for an E-selectin and CXCR4 inhibitor like GMI-1359 to molecularly excise disseminated breast cancer cells.1

"The initiation of enrollment is an important milestone in our exploration of GMI-1359 and its potential as a novel approach to treating metastatic cancer," said GlycoMimetics Senior Vice President of Clinical Development and Chief Medical Officer Helen Thackray, M.D., FAAP. "We’re pleased to have such distinguished researchers at Duke University begin to explore the use of this investigational therapy and look forward to learning more about its potential impact as clinical study advances."

More information on this clinical trial can be found at www.clinicaltrials.gov.

About GMI-1359

GMI-1359 is designed to simultaneously inhibit both E-selectin and CXCR4. E-selectin and CXCR4 are both adhesion molecules involved in tumor trafficking and metastatic spread. Preclinical studies indicate that targeting both E-selectin and CXCR4 with a single compound could improve efficacy in the treatment of cancers that involve the bone marrow such as acute myeloid leukemia and multiple myeloma or in solid tumors that metastasize to the bone, such as prostate cancer and breast cancer, as well as in osteosarcoma, a rare pediatric tumor. GMI-1359 has completed a Phase 1 clinical trial in healthy volunteers. The newly initiated Phase 1b clinical study in breast cancer patients is designed to enable investigators to identify an effective dose of the drug candidate and to generate initial biomarker data around the drug’s activity.

On January 30, 2020 University of Pennsylvania reported a scientific team is developing a new CAR T-cell gene therapy treatment for advanced metastatic prostate cancer with a $500,000 grant from Alliance for Cancer Gene Therapy (ACGT) (Press release, University of Pennsylvania, JAN 30, 2020, View Source [SID1234553699]).

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The ACGT grant was awarded to Joseph Fraietta, PhD, assistant professor of microbiology and a T-cell biologist with expertise in tumor immunology and translational medicine, and Naomi Haas, MD, director of the Prostate and Kidney Cancer Program, associate professor of medicine, and nationally renowned expert in the field of prostate and kidney cancer. The goal of the ACGT-funded study is to overcome prostate cancer’s stubborn resistance to CAR T-cell therapy, a therapy that has been successful in treating blood cancers. Drs. Fraietta and Haas are exploring approaches for re-engineering T-cells to enable them to induce safe, long-term remission for advanced, metastatic prostate cancer patients.

"The grant from ACGT will help us advance our clinical work in a very novel way," said Dr. Fraietta. "If we can unlock the epigenetic code that controls the fate and function of T-cells, it could be a game changer."

"The ACGT Scientific Advisory Council is impressed with the potential of this research team and their successful innovations in the use of T-cell therapy," noted Kevin Honeycutt, CEO and president of ACGT. "Because Drs. Fraietta and Haas are building on direct results already achieved with patients, there may be less transition time required to get a promising new treatment into the clinic for prostate cancer patients. Plus, we believe this research could provide a tumor-attack roadmap to help fight other cancers, including lung, pancreatic, ovarian and brain."

In the ACGT-funded study, Drs. Fraietta and Haas are going from the bedside back to the benchtop to employ new insight into how to better enable T-cells to battle cancer cells in solid tumors. Drs. Haas and Fraietta will explore the connection between nutrient availability and epigenetic programming, and how these factors influence the viability of T-cells and their anti-tumor functionality. This research builds on durable results being achieved by Dr. Haas in related prostate cancer clinical trials. In these trials, different doses of CAR T-cell gene therapies are being used to treat metastatic patients for whom traditional hormonal therapies, chemotherapies, radiation and surgery have failed.

"For so many years, chemotherapy, radiation and surgery were the traditional treatments for cancer. For prostate cancer, there’s also hormone therapy," said Honeycutt. "Unfortunately, as the cancer progresses, it often stops responding to these traditional treatments. New cell and gene therapy approaches like the ones Drs. Fraietta and Haas are employing offer new hope to all cancer patients. ACGT has been dedicated to funding innovative science that harnesses the power of cell and gene therapy and transforms how cancer is treated. The work of Drs. Fraietta and Haas is a great example of this promise."

ACGT has been instrumental in funding some of the decade’s most transformative research, including breakthroughs in the use of CAR T-cell gene therapy for leukemia by the University of Pennsylvania’s Carl H. June, MD. "Dr. June received his first ACGT grant in 2004 and a second in 2008, back when gene therapy was considered a risky proposition," says Honeycutt. "Fast forward to today and the field has changed dramatically with major pharmaceutical companies and research institutions vying for the next big discovery using gene therapy or immunotherapy."

On January 30, 2020 A discovery by University of North Carolina Lineberger Comprehensive Cancer Center researchers could allow scientists to fine-tune genetically engineered immune cells to heighten their killing power against tumors or to decrease their activity level in the case of severe side effects (Press release, Lineberger Comprehensive Cancer Center, JAN 30, 2020, View Source [SID1234553698]).

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Gianpietro Dotti is the Director of the Cancer Cellular Immunotherapy Program at UNC Lineberger.
UNC Lineberger’s Gianpietro Dotti, MD.

In a study published in Cancer Cell, researchers led by UNC Lineberger’s Gianpietro Dotti, MD, reported new findings about the regulation of co-stimulatory molecules that could be used to activate cancer-killing immune cells – chimeric antigen receptor T-cells, or CAR-T – or decrease their activity.

"In immunology, it’s always about balance; you don’t want to have too much T-cell activation, and you don’t want T-cell activation to be too low," said Peishun Shou, PhD, postdoctoral research associate at UNC Lineberger and the study’s co-first author. "We wanted to keep the T-cell activation and tumor killing at a suitable or sustainable level."

Cellular immunotherapy
Cellular immunotherapy, or CAR-T immunotherapy, involves extracting specific immune cells from patients, engineering the cells in the lab to hunt tumor cells displaying a specific molecular target, and then re-infusing them to fight their cancer.

Through the Clinical Immunotherapy Program, UNC Lineberger researchers have designed novel investigational CAR-T therapies for Hodgkin and non-Hodgkin lymphoma, multiple myeloma, neuroblastoma and leukemia that are being studied in clinical trials.

"We are conducting and developing clinical studies with CAR-T cells in both liquid and solid tumors. In these studies, we are testing what we call the ‘new generation’ of CAR-T cells, hoping to further enhance the therapeutic index of this technology," said Dotti, the study’s corresponding author, a professor in the UNC School of Medicine Department of Microbiology and Immunology and director of the UNC Lineberger Cellular Immunotherapy Program. "This latest study highlights how when translational and basic science come together, we can hopefully improve therapeutic strategies."

CAR-T immunotherapy study findings
In the Cancer Cell study, researchers revealed new strategies for engineering investigational CAR-T to either increase the activity of modified T-cells to more effectively kill tumor cells, or decrease their activity in case the therapies trigger severe side effects.

They developed strategies for improving two different types of modified T-cells. These two types of CAR-T cells are differentiated by the signals that activate them. First, they have a receptor that recognizes a specific marker on the tumor – the first signal. They also need a second signal that helps to fully activate them and increase their response. There are two different types of T-cells that have different "second signals" that activate them.

Peishun Shou is a postdoctoral researcher at UNC Lineberger.
UNC Lineberger’s Peishun Shou, PhD.
One type of CAR-T is co-stimulated by the CD28 protein, and another is stimulated by 4-1BB. UNC Lineberger researchers wanted to find a way to regulate these proteins in order to "fine-tune" the cells’ disease-fighting response, since researchers reported each type of CAR-T has differences in terms of how long it typically lasts in the body to fight cancer, how quickly it responds and the strength of its response.

"T-cells have to be activated to kill tumor cells," Shou said. "If you have better activation, you have more cytokine release … and the cells can better target a tumor and kill it. In some cases, we want to make the T-cells stronger, more active, and depending on the tumor type, we may want to tune down the T-cell activation to help the T-cells survive and expand."

For CAR-T co-stimulated by 4-1BB, scientists found they could increase expression of the LCK molecule to increase the cells’ activity.

"What we found is that the LCK molecule can bind to the CAR, enhancing the CAR-T cell activation and signaling transduction, which therefore will help CAR-T cells get a better tumor-killing effect," Shou said.

CAR-T safety switch feature
They also reported on the discovery of a new "safety switch" mechanism to reduce activity of CAR-T co-stimulated by CD28. Doctors could use the safety switch should patients experience severe side effects from the experimental therapy.

They found they could use a molecule called SHP1 to reduce T-cell activity. When they added a certain drug, SHP1 bound to the CAR to reduce the activity of CAR-T cells.

"In the presence of the drug, we can cool down or tune down the CAR-T cell activation," Shou said. "The advantage of this switch is that it will not kill the CAR-T cells; it’s just temporarily tuning down the activity."

Researchers want to investigate using these findings to improve CAR-T treatments against blood cancers like leukemia, and to potentially improve experimental treatments for solid tumors.

"Researchers in the CAR-T immunotherapy field now want to solve the solid tumor problem," Shou said. "Solid tumors have an immunosuppressive microenvironment, so you need stronger CAR-T activation."

On January 30, 2020 Corcept Therapeutics Incorporated (NASDAQ: CORT), a commercial-stage company engaged in the discovery and development of drugs to treat severe metabolic, oncologic and neuropsychiatric disorders by modulating the effects of the stress hormone cortisol, reported preliminary fourth quarter revenue of $87.9 million, compared to $66.8 million in the fourth quarter of 2018 (Press release, Corcept Therapeutics, JAN 30, 2020, https://ir.corcept.com/news-releases/news-release-details/corcept-therapeutics-announces-fourth-quarter-and-full-year-2019 [SID1234553696]). Preliminary 2019 revenue was $306.5 million, an increase of 22 percent from 2018.

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Cash and investments increased by $48.4 million in the fourth quarter, to $315.3 million.

These results are prior to completion of the company’s annual independent audit and are subject to adjustment.

Corcept projects 2020 revenue of $355 – 375 million.

"Our Cushing’s syndrome business had an excellent year," said Joseph K. Belanoff, MD, Corcept’s Chief Executive Officer. "As awareness of the poor health outcomes associated with hypercortisolism increased and physicians screened more patients for Cushing’s syndrome, the number of patients receiving Korlym grew. We expect that growth to continue."

"Korlym’s commercial success has given us the resources to develop our proprietary selective cortisol modulators in a wide range of serious disorders," added Dr. Belanoff. "These compounds represent Corcept’s future. We look forward to an important year."

"Our program in Cushing’s syndrome is the most advanced," said Andreas Grauer, MD, Corcept’s Chief Medical Officer. "The pivotal trial of Korlym’s planned successor, relacorilant, is actively enrolling patients at sites in the United States, Europe and Israel. We are also launching a Phase 3 trial in patients whose Cushing’s syndrome is caused by adrenal adenomas.

"Our programs in metabolic and oncologic disorders are poised to advance significantly. In the second quarter, we will have results from the second part of our Phase 1b trial of miricorilant for the prevention of antipsychotic-induced weight gain (APIWG). Miricorilant’s Phase 2 trial for the reversal of recent APIWG continues to accrue patients. We plan to start two additional Phase 2 trials – one for the reversal of long-standing APIWG and another for the treatment of patients with non-alcoholic steatohepatitus (NASH) – by year-end.

"Our Phase 2 trial of relacorilant to treat advanced ovarian cancer continues to enroll patients at sites in the United States and Europe," added Dr. Grauer. "In the second quarter, we anticipate starting a Phase 3 trial of relacorilant in metastatic pancreatic cancer and a Phase 1b trial of relacorilant combined with an immunotherapeutic agent in adrenal cancer. By year-end, we expect to conclude the dose-finding trial of our proprietary cortisol modulator exicorilant in combination with enzalutamide in castration-resistant prostate cancer."

Hypercortisolism

Hypercortisolism, often referred to as Cushing’s syndrome, is caused by excessive activity of the hormone cortisol. Endogenous Cushing’s syndrome is an orphan disease that most often affects adults aged 20-50. In the United States, an estimated 20,000 patients have Cushing’s syndrome, with about 3,000 new patients diagnosed each year. Symptoms vary, but most patients experience one or more of the following manifestations: high blood sugar, diabetes, high blood pressure, upper-body obesity, rounded face, increased fat around the neck, thinning arms and legs, severe fatigue and weak muscles. Irritability, anxiety, cognitive disturbances and depression are also common. Hypercortisolism can affect every organ system in the body and can be lethal if not treated effectively.

On January 30, 2020 Applied DNA Sciences, Inc. (NASDAQ: APDN), reported that it plans to release financial results for its fiscal 2020 first quarter ended December 31, 2019 after market close on Thursday, February 6, 2020. In conjunction with the release, the Company has scheduled a conference call at 4:30 p.m. Eastern Time that will also be broadcast live over the Internet (Press release, Applied DNA Sciences, JAN 30, 2020, View Source [SID1234553695]).

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What: Applied DNA’s Fiscal 2020 First Quarter Financial Results Conference Call
When: Thursday, February 6, 2020, at 4:30 p.m. Eastern Time
Where: Via phone by dialing +1 844-887-9402 or +1 412-317-6798 and ask to join the Applied DNA call; via webcast.

A telephonic replay of the conference call will be available for one day and may be accessed by calling +1 877-344-7529 or +1 412-317-0088 with the passcode 10138146. The webcast will be archived within the ‘Events and Presentations’ portion of the ‘Investors’ page to the company’s website.